Fecal microbiota transfer to improve diabetes control post-bariatric surgery

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients, Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

16 Jan 2024 → ongoing

Decision date (initial)

2024-11-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Direction Générale de l’Offre des Soins du Ministère de la santé et de la prévention

External identifiers

EU CT number

2024-511870-65-00

EudraCT number

2019-003841-13

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To assess Fecal microbiota transfer (FMT) efficacy on Hba1c change from baseline to 6 months (6M=24W) follow-up, in non-diabetic Remission (NDR) patients who underwent Bariatric surgery (BS) 1 to 5 years ago.

Secondary objectives 18

1. Evaluate FMT efficacy on the Hba1c change from baseline within the 2 years of follow-up,
2. Evaluate FMT efficacy on the change in endogen insulin production via the change in C peptide from baseline to 2 years of follow-up
3. Evaluate FMT efficacy on the change in insulin resistance from baseline to 24W
4. Evaluate FMT efficacy on the change in holter glycemic profile at 6W and 24W
5. Evaluate FMT efficacy on the number and type of anti-T2D drugs (if Hba1c does not change) from baseline to 1 and 2 years
6. Evaluate FMT efficacy on the number of patients achieving partial or complete DR at 24W
7. Evaluate FMT efficacy on the number of patients achieving at 24W and maintaining partial or complete DR at 1 and 2 years
8. Evaluate FMT efficacy on the proportion of patients needing a “safety” glucose lowering treatment to control Hba1c in both groups (despite FMT or placebo transfer)
9. In the FMT group: describe how long the FMT effects last (i.e. time with 1st HbA1c at least 0.15% lower than baseline value)
10. In the FMT group : describe how many FMT cures are needed to obtain the primary end-point (-0.75% reduction of Hba1c)
11. Evaluate the proportion of good responders’ patients
12. Identify characteristics of good response related to the receiver
13. – Identify characteristics of good response related to good donor’s (i.e. factors from the donor associated with good response in the receiver)
14. Identify gut microbiota signature
15. Changes in gut microbiota MGR and microbiota composition
16. Changes in systemic gut microbiota related metabolites
17. Evaluate FMT safety
18. Evaluate quality of life after FMT

Conditions and MedDRA coding

Adults Non Diabete Remission (NDR) Type 2 Diabete (T2D) patients 1 to 5 years after bariatric surgery

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. For patients : Adult patients from 18-65 years old
2. For patients : T2D patients any severity of initial T2D disease before BS
3. For patients : Who underwent Bariatric surgery (BS) 1 to 5 years before (Roux-en-Y gastric bypass or sleeve, patients with pre-BS BMI≥35kg/m²)
4. For patients : Non-Diabetic remission (NDR) patients 1-year post-BS, defined as Hba1c>6.5% and/or fasting glycaemia>6.9mmol/l and/or receiving anti-diabetic drugs for at least 2 months. We will rather select patients with uncontrolled diabetes with Hba1c>7% and willing to receive proton pump inhibitor (PPI)
5. For patients : Patient compliant to 1rd year follow-up post-BS (who came to at least 2 among the three routine care follow-up visits during the first year (i.e. 3, 6 and 12M)
6. For patients : Signature of the informed consent
7. For patients : Affiliated to a social security regime (except AME)
8. For donors : Age ≥ 18 years and < 50 years
9. For donors : Lean individuals (18
10. For donors : Euglycemic: fasting glycemia <6mmol/l; Hba1c <5.9%
11. For donors : Healthy no current drug prescription (except contraception or pain killers other than AINS)
12. For donors : Regular bowel movement in the morning defined as 1 stool/day at least
13. For donors : Signature of the informed consent
14. For donors : Subject with health insurance (except AME)

Exclusion criteria 20

1. For patients : Type 1 diabetes
2. For patients : Patient deprived of their liberty by a judicial or administrative decision
3. For patients : Patients receiving antibiotics (ATB) at the selection time or within the 3 previous months (if agreeing to participate to the study, the patients will be proposed randomization 3 months after stopping ATB)
4. For patients : Immunosuppressive therapy
5. For patients : Laxative treatments
6. For patients : DR since BS (nor relapse patients detailed further in the protocol)
7. For patients : Patients already recruited in another interventional studies study where a drug is being tested
8. For patients : Pregnant or breastfeeding women
9. For patients : Patient with contemporary disease such as intestine disease
10. For patients : Patient under guardianship or curatorship
11. For donors : Familial history of obesity or diabetes and personal history of overweight/obesity
12. For donors : Infectious risk (for more information see the protocol)
13. For donors : Gastrointestinal disease (for more information see the protocol)
14. For donors : Personal or 1st degree family history of autoimmune or inflammatory disease (inflammatory arthritis, psoriasis, multiple sclerosis, type I diabetes, Hashimoto…)
15. For donors : Factors that may affect the composition of the intestinal microbiota (Special Diet - exclusion diet, vegetarian diet) /Taking immunosuppressants - eg calcineurin inhibitors, corticosteroids, biological agents, etc. / Chemotherapy / Subject with a chronic illness / Curative long-term treatment
16. For donors : Exclusion criteria according screening test : 1/Positive result for one of the contagious diseases testing blood and stool, excepting for IGG positive EBV, CMV and toxoplasma serology according to ANSM recommendations and only positive Ac HBS HBV witness of post-vaccination immunity and HAV Healed / 2 - Carrier of multiresistant bacteria / 3- - Abnormal biological test at inclusion suggesting a pathology: fasting blood glucose, Hba1c, blood count, chemistry panel with determination of urea and creatinine, liver function tests (AST, ALT, GGT, PAL, bilirubin), CRP, hemostasis
17. For donors : Pregnancy or breastfeeding women
18. For donors : Subject under guardianship or curatorship
19. For donors : Subject deprived of their liberty by a judicial or administrative decision
20. For donors : Temporary donor’s exclusion criteria - Infectious risk (for mors information see protocol)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Hba1c change from baseline to 6 months post randomization (we expect at least -0.75%)

Secondary endpoints 19

1. Evolution of Hba1c from baseline to 2 years post randomization Hba1c will be measured at the following visits: baseline 6, 12, 18, 24W, 1 and 2 years post randomization
2. Evolution of C-peptide from baseline to 2 years post randomization C-peptide will be measured at the following visits: baseline 6, 12, 18, 24W, 1 and 2 years post randomization
3. Evolution of insulin secretion from baseline to 24W using the HOMA-B calculator (=20 × fasting insulin (μIU/ml)/ fasting glucose (mmol/ml) − 3.5)
4. Evolution of insulin resistance from baseline to 24W: we will use the HOMA-IR (= fasting insulin (μIU/ml) × fasting glucose (mmol/ml)/ 22.5) and Disse index (=Disse 12*((2.5*(HDL-total cholesterol)-NEFA)-insulin)) which are two complementary markers to evaluate insulin resistance using different parameters.
5. Glycaemia profile (using glycemic holter) changes from baseline to 6W and 24W
6. Number of antiT2D drugs. The number of concomitant anti-diabetic drugs will be analysed at baseline and at 1 and 2 years’ post-randomization.
7. Type of antiT2D drugs. The type of anti-diabetic drugs will be analysed at baseline and 1 and 2 years’ post-randomization, modifications will be described.
8. Number of patients reaching DR. Proportion of patients reaching DR (partial or complete) at 24W and maintaining it at 1 and 2 years. Partial diabetes remission (PDR) is defined as Hba1c <6.5% and FPG <7.0 mmol/l without the need of glucose- lowering agents. Complete diabetes remission (CDR) is defined as Hba1c <6.0% and FPG <5.6 mmol/l without glucose-lowering agents
9. Proportion of patient needing a “safety” glucose lowering treatment to control Hba1c despite FMTs
10. Describe how long the FMT effects last (i.e. time with 1st HbA1c at least 0.15% lower than baseline value)
11. Describe how many FMT cures are needed to obtain the primary end-point (-0.75% reduction of Hba1c)
12. Evaluate the proportion of good responders’ patients (Good responders are defined in the protocol)
13. Identify characteristics of good response related to the receiver (more detail in protocol)
14. Identify characteristics of good response related to good donor’s (i.e. factors from the donor associated with good response in the receiver)
15. Identify gut microbiota signature (i.e. dominant/subdominant bacteria/taxa/ genus/ species) associated with good response of FMT, in the receiver post-FMT (at 6 and 12W) (metagenomic analysis as described above)
16. Changes in gut microbiota MGR and microbiota composition in receivers from baseline to 6, 18 and 24W follow-up (with further comparison between good/bad responders)
17. Changes in systemic gut microbiota related metabolites (LC-MS metabolomics) from baseline to 6, 18 and 24W)
18. Evaluate FMT safety (more detail in protocol)
19. Evaluate changes in quality of life after capsulized FMT (baseline vs. after FMT and between treatment groups using SF36 questionnaire)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Coordinating Investigator

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Coordinating Investigator

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications